Related Experiment Videos
A cerebral nitrergic pathway modulates endotoxin-induced changes in gastric motility
E Quintana1, E García-Zaragozá, M A Martínez-Cuesta
1Department of Pharmacology, Faculty of Medicine, University of Valencia, Avd. Blasco Ibáñez 15, 46010 Valencia, Spain.
British Journal of Pharmacology
|September 21, 2001
Summary
Low-dose endotoxin inhibits gastric motor function by activating capsaicin-sensitive neurons and neuronal nitric oxide synthase (NOS) in the brainstem. This pathway involves the dorsal vagal complex and Fos expression, highlighting a key neural mechanism.
Area of Science:
- Neurogastroenterology
- Physiology
- Pharmacology
Background:
- Stress and endotoxins can significantly alter gastric motor function.
- The specific neural pathways mediating these effects are not fully understood.
- Nitric oxide synthase (NOS) is implicated in various physiological processes, including gastrointestinal regulation.
Purpose of the Study:
- To elucidate the neural mechanisms by which endotoxin modulates gastric motor function.
- To investigate the role of afferent neurons and nitric oxide synthase in endotoxin's effects on gastric tone.
- To examine the central nervous system's involvement, specifically Fos expression in the dorsal vagal complex.
Main Methods:
- Systemic administration of endotoxin and 2-deoxy-D-glucose (2-DG) in urethane-anesthetized rats.
- Functional inhibition of afferent neurons using capsaicin.
- Pharmacological inhibition of nitric oxide synthase (NOS) using N(G)-nitro-L-arginine methyl ester (L-NAME).
- Immunohistochemical analysis for Fos expression in the dorsal vagal complex (DVC).
- Measurement of Ca(2+)-dependent nitric oxide synthase (cNOS) activity in brainstem tissue.
Main Results:
- Low-dose endotoxin prevented the 2-DG-induced increase in gastric tone.
- Capsaicin pretreatment blocked the inhibitory effects of endotoxin, indicating the involvement of capsaicin-sensitive afferent neurons.
- L-NAME administration (intravenous and intracerebroventricular) also prevented endotoxin's inhibitory effects.
- Endotoxin increased Fos expression in the nucleus tractus solitarii (NTS) and dorsal motor nucleus (DMN) of the DVC, an effect blocked by L-NAME.
- Endotoxin elevated Ca(2+)-dependent NOS activity in the brainstem, but not in the stomach.
Conclusions:
- The inhibition of gastric motor function by low-dose endotoxin involves the activation of capsaicin-sensitive afferent neurons.
- Neuronal nitric oxide synthase (NOS) in the brainstem plays a critical role in this endotoxin-induced pathway.
- The findings identify a specific neural circuit in the brainstem mediating the effects of endotoxin on gastric function.